Pathophysiology Chapter 3 Objectives

Epigenetics

Modification of gene expression without changes to DNA sequence. The study of mechanisms that will switch genes on or off. An emerging field of science that studies heritable changes caused by the activation and deactivation of genes without any change in

DNA Methylation

Epigenetic Mechanism. Results from attachment of methyl group to cytosine. Renders genes silent. Prominent role in health and disease. Aberrant Methylation can lead to misregulation(impairs) of tumor-suppressor genes(anti-oncogenes-protects cells from can

Histone Modifications

Epigenetic Mechanism. Histones-proteins that facilitate compaction of DNA into the nucleus of a cell. Histone modifications include histone acetylation and deacetylation to the end of a histone protein. (if this doesn't occur, congenital heart disorders w

RNA-Based Mechanisms

Epigenetic Mechanism. Noncoding RNAs (ncRNAs)-Role in RNA splicing and DNA replication. MicroRNAs (miRNAs)-too little coding. Modulate the stability and transactional efficiency of existing messenger RNAs. Oncomirs-miRNAs that stimulate cancer development

Imprinting

For some human genes, a given gene is transcriptionally inactive on only one copy of a chromosome. (i.e. Copy inherited from father is active while copy inherited from mother is inactive (silenced). Transcriptionally silenced genes are said to be "imprint

Diseases caused by abnormal imprinting patterns

Imprinting of maternally inherited genes tends to reduce offspring size (i.e Angelman syndrome). Imprinting of paternally inherited genes tends to increase offspring size. (i.e. Prader-Willi syndrome).

Compare and contrast the molecular and phenotype features of Prader-Willi and Angelman syndromes

A well known disease example of imprinting is associated with deletion of 4 million base pairs of long arm of chromosome 15. Manifestations of Prader-Willi syndrome if inherited from father: Short stature, hypotonia, small hands and feet, obesity, mentall

Beckwith-Wiedemann Syndrome

20-30% caused by inheritance of two copies of a chromosome from father and no copies from mother. Overexertion of active insulin-like growth factor 2 (IGF-2). Manifestations present at birth: large for gestational age, neonatal hypoglycemia, large tongue,

Environmental factors that can have long-term impacts on epigenetic states

1. Relationship between nutritional deprivation and disease on one or more generations is largely unknown. Ig-f 2 possible target of epigenetic modifications arising through nutritional deprivation. In utero exposure to chemicals may lead to similar epige

Strategies for reversing epigenetic modifications

Unlike DNA sequence mutations, epigenetic modifications can be reversed through pharmaceutical intervention. Agents may reverse changes associated with disease phenotype. DNA demethylating agents (5-azacytidine)-(has been used as a therapeutic drug in the

Genetic Screening

The process of testing a population for a genetic disease in order to identify a subgroup of people that either have the disease or the potential to pass it to their offspring

Epigenetic screening for cancer

Shows promise as a tool for early cancer diagnosis. The best evidence of epigenetic effects on disease risk comes from studies of human cancer.

Genetic Testing

Is the use of a laboratory test to look for genetic variations associated with a disease. The results of testing can be used to confirm or rule out a suspected genetic disease or to determine the likelihood of a person passing on a mutation to their offsp

Why are pairs of identical twins especially useful in the study of epigenetic phenomena?

As twins age, they demonstrate increasing differences in methylation patterns of their DNA sequences, causing increasing numbers of phenotypic differences. In studies of twins with significant lifestyle differences, large numbers of differences in their m